This application proposes to plan a multicenter trial of corticosteroids in boys with Duchenne muscular dystrophy. The corticosteroid prednisone is of established 18 months benefit to strength in Duchenne dystrophy, and another corticosteroid, deflazacort, may also be of benefit. Many different regimens have been developed because of concerns regarding side effects and long-term risk/benefit, resulting in great inconsistency of practice. Defining the optimum regimen is a stated NIH priority; this proposal has been developed in response to PA-05-038 (Muscular Dystrophy- pathogenesis and therapy). The proposed randomized controlled trial will compare 3 corticosteroid regimens to address the pragmatic hypothesis that daily corticosteroid (prednisone or deflazacort) will be of greater benefit in terms of function and patient/parent satisfaction than intermittent corticosteroid (prednisone). The primary statistical analysis will be based on a multivariate (3-dimensional) outcome (time to rise from the floor, forced vital capacity, and treatment satisfaction) and a global test of the null hypothesis that the corticosteroid regimens do not differ with regard to any of the three outcomes vs. the alternative that they differ (in the same direction) with regard to at least one of the outcomes. We also hypothesize that daily deflazacort will have a preferable side effect profile to that of daily prednisone. The trial will randomize 300 boys aged 4-7 years to 0.75 mg/kg/d prednisone; 0.9 mg/kg/d deflazacort; or 0.75 mg/kg/d prednisone for 10 days alternating with 10 days off. Secondary outcome variables will include regimen tolerance, other timed function tests; cardiac function, quality of life, caregiver burden, and adverse event profile. Participants will be recruited over a 2 year period and followed for at least 3 years. The study protocol includes standardized regimens for treatment and prevention of bone, cardiac, behavioral, and cushingoid complications of Duchenne dystrophy and corticosteroids. Planning phase activities include establishing data management/communication and patient monitoring strategies; test/retest reliability assessment; preparation of operations manual; translation of assessment tools; confirming the achievability of recruitment targets; and finalizing details of drug distribution and plans for data and safety monitoring. This trial will assess which of the 3 regimens is optimum for treatment of Duchenne dystrophy and provide novel information on longer-term corticosteroid side effects. It will provide the basis for the long-term (8-10 year) study of the relative efficacy and tolerability of corticosteroid regimens with the primary outcome variable of time to loss of ambulation. Lay Summary: This project will plan a study to determine the best dosage and schedule of treatment for use of corticosteroids in Duchenne muscular dystrophy and will help to standardize approaches to prevent complications of Duchenne dystrophy and its corticosteroid treatment.